Ghrelin mediated neuroprotection - A possible therapy for Parkinson's disease?

Abstract

Parkinson's disease is a common age-related neurodegenerative disorder affecting 10 million people worldwide, but the mechanisms underlying its pathogenesis are still unclear. The disease is characterised by dopamine nerve cell loss in the mid-brain and intra-cellular accumulation of α-synuclein that results in motor and non-motor dysfunction. In this review, we discuss the neuroprotective effects of the stomach hormone, ghrelin, in models of Parkinson's disease. Recent findings suggest that it may modulate mitochondrial function and autophagic clearance of impaired organelle in response to changes in cellular energy balance. We consider the putative cellular mechanisms underlying ghrelin-action and the possible role of ghrelin mimetics in slowing or preventing Parkinson's disease progression. This article is part of the Special Issue entitled 'Metabolic Impairment as Risk Factors for Neurodegenerative Disorders.'

Insulin Signaling Impairment in the Brain as a Risk Factor in Alzheimer’s Disease

“…Mitochondrial activity and genesis were improved. Importantly, the chronic inflammation response in the brain was much reduced by the drug (Bayliss et al, 2016a,b; Morgan et al, 2018). These impressive effects make ghrelin a candidate to be a novel treatment for PD.…”

Multiple Beneficial Effects of Ghrelin Agonist, HM01 on Homeostasis Alterations in 6-Hydroxydopamine Model of Parkinson’s Disease in Male Rats

“…In particular, ghrelin receptors are expressed in SN neurons immunoreactive for tyrosine hydrolase (TH; Guan et al, 1997; Zigman et al, 2006; Jiang et al, 2008; Andrews et al, 2009) and are downregulated at this site in a mouse model of PD with motor dysfunction (Suda et al, 2018). Other studies indicate that ghrelin modulates dopaminergic neurons in the ventral tegmental area (VTA) and SN (Stievenard et al, 2017) and induces a neuroprotective effect in animal models of PD (Bayliss and Andrews, 2013; de Candia and Matarese, 2018; Morgan et al, 2018). In addition, clinical studies indicate that systemic or oral administration of ghrelin agonists increases appetite and body mass in patients with cancer cachexia (Argilés et al, 2017; Khatib et al, 2018).…”

The Impact of Ghrelin on the Survival and Efficacy of Dopaminergic Fetal Grafts in the 6-OHDA-Lesioned Rat

“…It is elevated during calorie restriction, a response unique amongst gastrointestinal hormones but interesting because calorie restriction has been linked to lower predisposition to neurodegenerative disease both in patients and animal models of disease (Maalouf et al, 2009). This neuroprotective activity may derive from a range of possible mechanisms, including anti-apoptotic, anti-oxidant, anti-inflammatory actions as well as boosting mitochondrial function (Morgan et al, 2017). Through raising levels of the uncoupling molecule 2 (UCP2), ghrelin increases the number of mitochondria and improves their respiration levels as well as widening the cellular buffering capacity to the reactive oxygen species (ROS) during stress (Andrews et al, 2009).…”